Safety and Activity of SNX-5422 Plus Ibrutinib in CLL

• Status: Withdrawn
• Trial end date: 2018-07-01
• Target enrollment: 0
• Participant gender: All

Summary

SNX-5422 is a prodrug of SNX-2112, a potent, highly selective, small molecule inhibitor of the molecular chaperone heat shock protein 90 (HSP90). Hsp90 inhibitors may overcome ibrutinib resistance in Mantle cell lymphomas and this study will investigate whether the addition of SNX-5422 to an established dose of ibrutinib will result in the removal of mutated BTK from blood mononuclear cells and/or prevents or delays disease progression of subjects with CLL

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Esanex Inc.

Criteria

Inclusion Criteria:

• Males or non-pregnant, non-breastfeeding females 18 years-of-age or older

• A diagnosis of CLL as defined by IWCLL 2008 criteria and currently on treatment with ibrutinib without evidence of disease progression.

• No more than 4 prior lines of anti leukemia therapy (not including ibrutinib)

• Presence of mutated BTK in ≥ 4% of peripheral blood or bone marrow CLL cells, or ≥1% and rising on two separate measurements obtained at least 28 days apart.

• Life expectancy of at least 9 months

• Karnofsky performance score 70

• Adequate baseline laboratory assessments

• Signed informed consent form

• Recovered from toxicities of previous anticancer therapy to CTCAE Grade ≤ 1 with the exception of alopecia

• Subjects with reproductive capability must agree to practice adequate contraception methods.

Exclusion Criteria:

• Subjects experiencing toxicity with ibrutinib

• Prior treatment with any Hsp90 inhibitor.

• Major surgery or significant traumatic injury within 4 weeks of starting study treatment.

• Conventional chemotherapy or radiation within 4 weeks.

• The need for treatment with medications with clinically-relevant metabolism by the cytochrome P450 (CYP) 3A4 isoenzyme within 3 hours before or after administration of SNX-5422

• Screening ECG QTc interval 470 msec for females, 450 msec for males.

• At increased risk for developing prolonged QT interval unless corrected to within normal limits prior to first dose of SNX-5422

• Patients with chronic diarrhea or with Grade 2 or greater diarrhea despite appropriate medical management.

• Gastrointestinal diseases or conditions that could affect drug absorption

• Gastrointestinal diseases that could alter the assessment of safety, including irritable bowel syndrome, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.

• History of documented adrenal dysfunction not due to malignancy.

• History of chronic liver disease.

• Active hepatitis A or B.

• Current alcohol dependence or drug abuse.

• Use of an investigational treatment (except for ibrutinib) from 30 days prior to the first dose

• Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination that are considered clinically important by examiner.

• Psychological or social reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.